Reflex circulatory collapse following intrapulmonary entrapment of activated platelets: mediation via 5‐HT₃ receptor stimulation

Abstract

1 The role of 5-HT2 and 5-HT3 receptors in the mediation of direct and reflex vascular responses to intrapulmonary platelet activation was investigated. 2 Anaesthetized rabbits were challenged intravenously with an emulsion of autologous bone marrow that produced a sharp increase in pulmonary blood pressure, a fall in systemic blood pressure, platelet consumption and death. 3 Platelet depletion before the challenge nearly abolished all the cardiovascular effects and prevented death. Bilateral vagotomy prevented the fall in systemic blood pressure and death but did not prevent the increase in pulmonary pressure. The intravenous administration of the 5-HT3 antagonist, MDL-72222, resembled the protection afforded by vagotomy whereas the 5-HT2 antagonist, ketanserin, only reduced the increase in pulmonary pressure without affecting the systemic response or mortality. 4 The effects of intravenous 5-HT and of electrical stimulation of the cephalic ends of the cut vagi nerves were also explored. 5-HT injection increased the pulmonary vascular pressure but its effects on systemic blood pressure were variable. These responses were modified by the 5-HT antagonists in a manner that resembles their effects on bone marrow embolism. Afferent vagal stimulation produced a fall in systemic blood pressure that was not prevented by MDL-72222. 5 This study indicates that a centrally mediated reduction of peripheral vascular tone is the cause of the potentially lethal circulatory collapse that follows the intrapulmonary entrapment of activated platelets. This reflex is initiated by the action of 5-HT on 5-HT3 receptors in the lung.

Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT3 receptors

“…Vagal 5-HT 3 sensitive ®bres that mediate renal sympathoinhibition are present both in the heart (Veelken et al, 1990) and lung (Veelken et al, 1997;Lee & Morton, 1995;Leanos et al, 1995) of rats. Ang II might interact locally with these aerent ®bres, or with the neuronal cell bodies of those ®bres in the nodose ganglion (Bacal & Kunze, 1994;Allen et al, 1988).…”

Witnessed asystole during spinal anesthesia treated with atropine and ondansetron: a case report

“…21 Furthermore, in a hemorrhagic rabbit model, granisetron was effective at preventing inappropriate HR slowing and allowed significantly more blood to be removed before reaching the target BP compared to the saline control. 10 Interestingly, non-cardiac 5-HT 3 receptors have been demonstrated also in the rat lung, 23 gastrointestinal mucosa 24 and rabbit carotid sinus. 25 All could be blocked with 5-HT 3 antagonists to prevent bradycardia and hypotension induced by 5-HT or phenyl biguanide (a 5-HT 3 agonist).…”

“…The survival rate reached 100% in the MDL 72222 group vs 25% in the saline group. 23 If this applies to humans as well, 5-HT 3 chemoreceptor stimulation by release of 5-HT from platelets may explain the sudden bradycardia and hypotension sometimes seen during cemented hip arthroplasty (often done under spinal anesthesia), and 5-HT 3 antagonists may have a potential therapeutic role.…”

“…11,16,22 Activated platelets appear to be a source of 5-HT in animal models 23,25,26 and epinephrine is well known to activate platelets. In some volunteers it has been demonstrated that catecholamine levels were elevated and platelets were depleted of their 5-HT content, suggesting that elevated concentrations of circulating catecholamines may induce platelet activation and 5-HT release.…”

Bimodality of cardiac vagal afferent C-fibres in the rat

“…The sympathoinhibitory response to PBG is abolished by specific 5HT 3 receptor blockers [24,28]. The response to PBG in the rat is mediated by vagal afferent fibres, mainly from the heart [23], although pulmonary C-fibres do play a role in the rat [13,26]. The endogenous ligand of the 5HT 3 receptor, serotonin, is present locally in the heart and is likely to be released from platelets in certain pathophysiological conditions [7,29].…”